If you are hesitating between 'Orientalism' and 'Culture and Empire', 'Orientalism' is probably the book to get. It was Saïd's first and original contribution, and it is about culture, his field, more than about history, in which he was not a specialist.
Saïd argues that Orientalism paved the ground for, and was later sustained by, colonialism in that it created fixed categories by which the Orient became known to Europeans. These stereotyped views emphasizing, say, fatalism, superstition, or a lack of a conception of liberty, predisposed Europeans to rule over the peoples they classified as Oriental. Saïd's point is that Orientalism owed more to textual analysis than to actual conditions in the East, enabling Europeans to project their own fantasies, wishes, and prejudices onto Orientals. History and archaeology, for example, interpreting the Orient through its classical cultures (ancient Egypt, Sanskrit, Sufi poetry, etc..), supported perceptions of Orientals as impervious to progress and at the same time of civilisations in decline and therefore in need of regeneration through European power. While some of Saïd's references are obscure, especially of some twentieth-century Orientalists, many draw from mainstream literature (Dante, Flaubert, Lane) or immediately graspable travel, historical, and political works. Most are entertaining and thought-provoking, sometimes hilarious, and Saïd's exegesis is consistently witty and incisive.
Saïd's is no doubt a partial view, and it has been criticized as well as emulated. But the author himself makes no total claim on his sources, many of which he professes to admire. This is a book about culture, not history: it brings to light a certain undercurrent in a body of work and literature, it does not aim to explain colonialism. (Indeed, this is probably why 'Orientalism' is less problematic than 'Culture and Empire': Saïd's work as history faces issues of chronology - Orientalism in art, for example, was in terminal decline when Britain and France began to grab the Middle East in earnest - and it is weaker at connecting representation to agency.) Finally, nor is 'Orientalism' about the evils of colonisation as such, or even the truthfulness of Orientalist writing. It is a decoding of a 200+ year-long academic and artistic tradition, no more or less. Saïd's interest is in studying Orientalism as cultural phenomenon, not an Orient which he argues is, as a category, mythical anyway. But it is best to quote the author: 'One scarcely knows what to make of these caricatural permutations of a book that to its author and in its arguments is explicitly anti-essentialist, radically sceptical about all categorical designations such as Orient and Occident, and painstakingly careful about not "defending" or even discussing the Orient and Islam.' This book is a must for anyone interested in the meaning of cultural difference, and it is an exhilarating, sometimes electrifying read.